Unverifiable mobile phone footage appeared to show the moment the crane fell, with a loud crash followed by panic and shouting.
Online activists created a hashtag on Twitter urging Mecca residents to donate blood at hospitals in the area.
No details were immediately available on the nationalities of the victims. Iran's official IRNA news agency, quoting the head of the Hajj Organisation, said that 15 Iranian pilgrims were among those injured.
The cause of the crane collapse was not confirmed, and official information was not forthcoming from the secretive kingdom.
The Saudi civil defence authority said on Twitter that emergency teams were sent to the scene after a "crane fell at the Grand Mosque."
The authority said an hour before the disaster that Mecca was "witnessing medium to heavy rains".
There were also reports of winds of more than 25mph that were blamed for toppling the crane. There have been strong sand storms in the region over the past week.
A photograph circulated on social media showed a crane next to the mosque being struck by lightening, but it was again not possible to confirm whether the image was genuine.
There are several other construction projects under way close to the Grand Mosque, which is spread across an 88 acre site. The crane was one of a number dotted around the site.
A major expansion of the Grand Mosque began last year in a bid to handle the huge numbers of visitors.
Last year more than two million people performed Hajj, while in 2012 the figure was more than three million.
A huge hotel complex is being built around a mile south of the Grand Mosque. The hotel, with 45 storeys and 10,000 bedrooms - including five floors for the sole use of the Saudi royal family - will be the largest in the world when it opens next year.
The governor of Mecca region, Prince Khaled al-Faisal, has ordered an investigation into the incident.
The pilgrimage, one of the largest religious gatherings in the world, this year takes place between September 21-26.
The official Saudi SPA news agency said in a statement that by yesterday, almost 800,000 pilgrims had arrived in the kingdom for Hajj.
The Grand Mosque is usually at its most crowded on Fridays, the Muslim weekly day of prayer.
The pilgrimage has been prone to disasters in the past, mainly from stampedes as pilgrims rushed to complete rituals and return home.
Up to 300 pilgrims died in such a stampede in 2006 and in 2004 a stampede killed more than 200. The worst stampede, in 1990, left 1,400 people dead.
In 2006, a concrete multi-story hotel collapsed, killing 76 people.
Saudi authorities have since gone to great lengths - and spent billions of pounds - to expand the main Hajj sites and improve Mecca's transportation system.
The mosque is Islam's most sacred site. At the heart of the mosque, the oldest parts of which date to the 16th century, is the Kaaba - a black cube-shaped building - which Muslims all over the world face when they pray. Hajj pilgrims perform a series of rituals, including walking anticlockwise seven times around the Kaaba.
- Daily Telegraph